Polymorphisms of alcohol metabolizing enzymes (ADH, ALDH) have been found to influence risk for alcohol dependence and heavy alcohol consumption. These polymorphisms are thought to influence alcohol behavior by altering the metabolism of alcohol, and influencing individual differences in alcohol response. Genetic variants in ADH and ALDH alleles occur at different rates in different ethnic groups. ADH/1B*3 alleles have been identified only in individuals of African decent and some Native American groups. In Native Americans, ADH1B*3 alleles have been found to protect against alcohol dependence. In African Americans, these alleles are negatively associated with family history of alcoholism, and protect against alcohol-related birth defects. The proposed project will test the role of ADH1B*3 alleles in the alcohol dependence risk process in African Americans. It is hypothesized that ADH1B*3 protects against alcohol dependence by influencing level of response to alcohol, and by influencing alcohol-related learning. One-hundred and thirty African American participants will be recruited for an alcohol challenge study. Participants will be genotyped for ADH1B, as well as additional ADH/ALDH polymorphisms. This sample size should be sufficient to obtain approximately 30 participants with ADH1B*3 alleles. Data on alcohol use, alcohol abuse/dependence symptoms, alcohol expectancies, family history of alcoholism and exposure to alcohol modeling in the family environment will be collected prior to the alcohol challenge visit. The proposed project has four principal aims. One is to test whether ADH1B*3 alleles are associated with increased response to alcohol in African Americans. Second, to test whether those with ADH1B*3 alleles differ in their alcohol expectancies. We will also test whether differences in expectancies are a function of differences in alcohol response and/or familial models of alcohol use. Finally, a mediation model will be tested, hypothesizing that the protective effect of ADH1B*3 alleles on alcoholism risk is mediated by differences in alcohol expectancies.